title: Role of CIP4 in high glucose induced epithelial--mesenchymal transition of rat peritoneal mesothelial cells.
abstract: BACKGROUND
  Peritoneal mesothelial cell (PMC) plays a key role in the process of peritoneal fibrosis. Epithelial-mesenchymal transition (EMT) of PMCs is an important mechanism of peritoneal fibrosis. Prolonged exposure to peritoneal dialysis fluid containing a high concentration of glucose may lead to EMT of PMCs. Cdc42-interacting protein-4 (CIP4) is a critical regulator of cell skeleton and downstream effector of Cdc42 and participates in EMT of tubular epithelial cells. In the present study, we investigate the possible role of CIP4 in EMT of PMC under high glucose (HG) condition in vitro and further explore the potential therapeutic point for peritoneal fibrosis.
  
  
  METHODS
  Rat peritoneal mesothelial cells (RPMCs) were isolated from the peritonea of rats by enzymatic digestion. Under HG conditions (1.5%, 2.5% and 4.25%), E-cadherin, α-SMA and CIP4 expression were assessed by Western blot. Effect of CIP4-siRNA and pcDNA3.1-CIP4 transfection on E-cadherin, α-SMA and CIP4 expression were also assessed respectively under 2.5% HG concentration. Cells were pretreated for 24 h with PI3K/Akt signaling inhibitor perifosine and effect of perifosine on CIP4 expression were detected by Western blot.
  
  
  RESULTS
  EMT induction by HG was confirmed by the prevalence of morphological changes, loss of E-cadherin, increase in α-SMA expression. CIP4-siRNA transfection can reverse EMT of RPMCs. Over-expression of CIP4 promoted characteristics similar to those commonly observed in EMT. Furthermore, the increased CIP4 in response to HG was efficiently inhibited by perifosine.
  
  
  CONCLUSIONS
  This study shows that CIP4 promotes high glucose-induced EMT through PI3K-Akt signaling pathway in RPMCs.
authors.affiliation: Department of Surgery, Affiliated Hospital of Medical College Qingdao University, 16 Jiangsu Road, Qingdao, Shandong Province, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: MeiSheng
authors.initials: M
authors.lastname: Bi
authors.forename: Feng
authors.initials: F
authors.lastname: Zhong
authors.forename: XueLong
authors.initials: X
authors.lastname: Jiao
authors.forename: DianLiang
authors.initials: D
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000737:chemistry; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D015778:Minor Histocompatibility Antigens; D010530:Peritoneal Dialysis / Q000009:adverse effects* / Q000379:methods; D056627:Peritoneal Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection
chemical_list: D000199:Actins; D015820:Cadherins; D015314:Dialysis Solutions; D005947:Glucose; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D010767:Phosphorylcholine; D034741:RNA, Small Interfering; C498640:Trip10 protein, rat; C498862:Acta2 protein, rat; C105905:perifosine